SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.

Vitamin D deficiency and obesity increases risk of testing positive for COVID-19.

• The COVID-19 positivity rate was higher in the 39,190 patients with “deficient”25(OH)D values (<50 nmol/L) (12.5%) than in the 27,870 patients with “adequate” values (75–85 nmol/L) (8.1%) and the 12,321 patients with values ³137.5 nmol/L (5.9%).
• The decrease in positivity rate associated with 25(OH)D levels appeared to plateau as values approached 137.5 nmol/L; COVID-19 positivity rates were similar between the 4,016 patients with values 137.5-147.5 nmol/L (6.0%) and the 8,305 patients with higher values (5.9%).
• COVID-19 positivity rates were significantly higher in the 9,529 patients from predominately black non-Hispanic zip codes (15.7%) and the 26,242 patients from predominately Hispanic zip codes (12.8%) than in the 112,281 patients from predominately white non-Hispanic zip codes (7.2%).
• Mean 25(OH)D levels were significantly higher in patients from predominately white non-Hispanic zip codes (82.5 ± 29.75 nmol/L) than in patients from predominately black non-Hispanic (72.75 ± 27.5 nmol/L) or Hispanic (72 ± 26.75 nmol/L) zip codes. Regression analysis indicated a strong correlation between 25(OH)D levels and COVID-19 positivity in each of these groups.
• Compared to the 67,667 patients age ³60 years, the 120,362 younger patients had significantly higher COVID-19 positivity (10.2% vs. 7.7%) and significantly lower mean 25(OH)D levels (73.5 ± 27 nmol/L vs. 88.5 ± 30.25 nmol/L).
• Compared to the 130,473 female patients, the 61,305 male patients had significantly higher COVID-19 positivity (10.7% vs. 8.7%) and significantly lower mean 25(OH)D levels (78.25 ± 28.5 nmol/L vs. 79.75 ± 29.5 nmol/L).

A total of 191,779 patients (median age = 54 years, range 40.4–64.7 years; 68% women) from all 50 US states with COVID-19 results from tests performed March 9, 2020 through June 19, 2020 and matching 25(OH)D results from the preceding 12 months were included.

• Causality cannot be concluded in the association between vitamin D status and the risk of COVID-19 because of this study’s retrospective design.
• Limitations of this study include that testing for COVID-19 was based on selection factors, including the presence and gravity of symptoms and exposure to infected individuals.
• High-risk groups, such as healthcare workers and first responders, were also more likely to be tested.
• Another limitation is that race/ethnicity estimates were based on aggregate U.S.Census proportions by zip code.
• There may be many other potentially confounding factors that were neither identified nor controlled for in this study.

These results demonstrate an inverse relationship between circulating 25(OH)D levels and COVID-19 positivity. For the entire population, those who had a circulating level of 25(OH)D <50 nmol/L had a 54% higher positivity rate compared to those who had a blood level of 75–85 nmol/L. The risk of COVID-19 positivity continued to decline until the serum levels reached 137.5 nmol/L. Northern and central latitudes, predominately Hispanic zip codes, predominately black non-Hispanic zip codes, age <60 years and male sex were independently associated with both 25(OH)D levels and COVID-19 positivity.

• This study is a retrospective, observational analysis of deidentified test results from a clinical laboratory, Quest Diagnostics.
• A Quest Diagnostics-wide unique patient identifier was used to match all results of COVID-19 testing performed March 9, 2020 through June 19, 2020, with 25(OH)D results from the preceding 12 months.
• Residential zip code data was also required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. Patient data were linked to estimated race/ethnicity proportions reported by zip code in the 2018 5-year American Community Survey (ACS). Latitude for each zip code, acquired from SAS reference data, was stratified into three groups: >40 degrees (“northern”); 32–40 degrees (“central”); or <32 degrees (“southern”).
• Total 25(OH)D measurements were categorized as follows: <50 nmol/L was ‘deficient’, 50–72.5 nmol/L was ‘suboptimal’, and ³75 nmol/L was ‘optimal’.
• Vitamin D seasonality was adjusted for with a model based on a previous 25(OH)D3 study, utilizing Quest Diagnostics results that fit the present study data well.

Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020 Sep 17;15(9):e0239252. doi: 10.1371/journal.pone.0239252. PMID: 32941512; PMCID: PMC7498100.